Modul–A Multicentre Randomised Clinical Trial of Biomarker-Driven Therapy for the 1St-Line Maintenance Treatment of Metastatic Colorectal Cancer (Mcrc): a Signal-Seeking Approach
Background: Many drugs active in mCRC target specific molecular aberrations or cell-signalling pathways and may only be effective in subsets of pts due to molecular differences between tumours. Molecular screening approaches and new biomarkers are required to fully characterize tumours, identify pts most likely to benefit, and predict treatment response. MODUL is a randomised, multicentre, active-controlled, open-label, parallel-group trial of biomarker-driven maintenance therapy for the 1st-line treatment of mCRC. The design permits future adaptation of current cohorts and inclusion of additional treatment cohorts based on novel evidence and corresponding compounds/combinations. Trial design: Eligible pts have measureable, unresectable disease with no prior chemotherapy for mCRC. The study has 3 phases: 1) Induction Treatment (approx. 4 months’ of FOLFOX + bevacizumab [bev]); 2) Maintenance Treatment; 3) Post-Treatment Follow-up. Eligible pts without progressive disease are assigned to a Maintenance Treatment cohort based on results of biomarker assessments obtained from tumour tissue. Current cohorts: Cohort 1–BRAF V600E mutated (BRAFmut); Cohort 2–‘No Biomarker’ cohort. Within each cohort, pts are randomized to either experimental treatment or control (2:1 basis): Cohort 1–experimental (fluoropyrimidine [FP], cetuximab, vemurafenib); Cohort 2–experimental (FP, bev, anti-PD-L1 antibody [MPDL3280A]). The control arm for all cohorts is FP + bev. Co-primary efficacy endpoints: early efficacy (≥20% reduction in tumour size after 2 months of Maintenance Treatment in first 27 pts of experimental arm); PFS (median and 4-month PFS rate from randomisation). Secondary efficacy objectives: overall survival; overall response rate; disease control rate; time to treatment response; duration of response. Safety assessment is based on adverse events, treatment modifications, and clinically significant laboratory values. Recruitment of 1680 pts is expected over approx. 3 years (total 6 years’ duration of trial) from sites in Europe, Asia, Africa, North America and South America. Disclosure: H. Schmoll: Consultant or Advisory Role (Roche) Research Funding (Roche); D. Arnold: Research funding (Roche) Scientific advisory board (Roche); A. De Gramont, M. Ducreux, A. Grothey, P.J. O'Dwyer and J. Tabernero: Scientific advisory board (Roche); B. Bendahmane, F. Hermann, C. Ingold, C. Mancao, S. Osborne and I. Statovci: Employment (Roche); E. Van Cutsem: Scientific advisory board (Roche).